Four groups of cDNA clones have been identified which detect transcripts which appear to be NK or NK and T cell specific. The first group identifies a transcript which appears to be selectively expressed in NK cells, the second and third groups identify transcripts expressed in NK and T cells, and the fourth group a transcript present in high levels in NK and T cells, but also present at low levels in B cells. Determination of the nature of the protein products encoded by the identified genes and their function, is likely to provide valuable insight into the mechanism of NK function. The intent of the proposed research is to: 1) identify additional cDNA clones which represent transcripts which are selectively expressed in NK or NK and T cells; 2) derived the sequences for the full length of the transcripts we have already identified; 3) analyze the role of the protein products encoded by these transcripts in NK and T cell function a) using antibodies raised against synthetic peptides corresponding to regions of the protein sequence derived from the DNA sequence, and b) using transfection of cDNA in both the sense and antisense orientations into appropriate cells, and subsequent analysis of cytolytic function in the resulting transfectants; 4) examine the mechanism of selective expression of the transcripts detected by the NK specific (group 1) cDNA clones by determining the potential involvement of tissue specific promoter and enhancer elements. By understanding how NK cells function, it may become possible to modulate their activity in vivo for both the treatment and prevention of cancer. The information gained from the studies proposed here should ultimately assist in the development of more effective strategies for cancer therapy.